Multi-omics reveal nuanced pathways in placental development

Abstract

<p>The placenta remains poorly studied despite being implicated in many pregnancy and chronic disorders. Trophoblast invasion and nutrient transport are critical placental processes where defects can lead to preeclampsia and other diseases. We set out to characterize protein pathways underlying those processes, using mouse as a model. We profiled the placenta proteome and phosphoproteome at embryonic day (e)7.5, when trophoblast invasion peaks, and at e9.5, when nutrient transport is occurring, and integrated this data with RNA-seq.</p> <p>Comparing the unmodified proteome and the transcriptome revealed that most upregulated proteins are not the result of transcript changes. However, genes upregulated at both levels reflected expected functions, such as enrichment of migration processes at e7.5 and of metabolic processes at e9.5. Proteins that were only upregulated at the protein level contained potentially novel genes involved in migration and patterning, and indicated that the placenta at e9.5 is under stress.</p> <p>The phosphoproteome revealed novel phosphosites on placental transcription factors (TFs) that were conserved in human and differentially phosphorylated in our dataset, indicating an important role for the sites in modulating TF function. When we combined the phosphoproteome with the other datasets, we found further clues that e9.5 placenta is a stressful environment, and we identified a posttranscriptionally and posttranslationally regulated network at this timepoint.</p> <p>This analysis provides a systems-level view of gene expression patterns at two critical timepoints of placental development, and opens the door for experimental validation of potentially novel proteins, phosphosites, and pathways that may be critical for normal placental function.</p>